Robert Rothbaum

A clinicopathologic study of enterocyte-adherent Escherichia coli : a cause of protracted diarrhea in infants.

Fifteen infants (age 3-28 wk) suffered from severe diarrhea with acute dehydration and poor growth. Persistent watery stools and suboptimal nutrition necessitated central venous alimentation with prolonged hospitalization. Repeated stool and small intestinal fluid cultures yielded the classical enteropathogenic Escherichia coli serotype 0119:B14. In all patients, biopsy of the jejunum or rectal mucosa, or both, showed moderate to severe damage, irregular atrophy of surface epithelium, and subnuclear vacuolization of crypt epithelium. Ultrastructural studies revealed bacteria adherent to mucosal cells with flattening of microvilli, loss of the cellular terminal web, and cupping of the plasma membrane around individual bacteria. Heavily colonized cells had marked intracellular damage. Assays for heat-labile, heat-stable, and vero cell toxins were negative for these Escherichia coli isolates. Oral neomycin and nutritional support resulted in clearing of Escherichia coli 0119:B14 from stool and small bowel with improvement in histologic characteristics. Damage to enterocytes and villi by adherent nontoxigenic Escherichia coli 0119:B14 results in protracted diarrhea in infants.

Evaluation of the pediatric crohn disease activity index: a prospective multicenter experience.

Background and Objectives: Longitudinal assessment of disease activity is necessary for studies of therapeutic intervention in children with Crohn disease. The Pediatric Crohn Disease Activity Index (PCDAI) was developed a decade ago for such a purpose, but it function has only been examined in a small number of studies with a limited number of patients. The primary objectives of the present study were to develop cut scores reflecting disease activity as determined by physician global assessment (PGA) and to evaluate the responsiveness of the PCDAI to changes in patient condition after therapeutic interventions. Methods: Data were derived from a prospective database of newly diagnosed children with inflammatory bowel disease established in 2002 at 18 pediatric gastroenterology centers in the United States and Canada. At diagnosis, at 30 days and 3 months after diagnosis, and quarterly thereafter, children (<16 years of age) with Crohn disease had disease assessment performed by PGA and PCDAI. Disease management was provided according to the dictates of the attending gastroenterologist and not by predetermined protocol. Results: 181 patients had concomitant PGA and PCDAI performed at diagnosis, and 95 of these had similar assessment at short-term follow up. Mean ± SD PCDAI scores for mild, moderate, and severe disease by PGA at diagnosis were 19.5 ± 10.4, 32.2 ± 12.7, and 47.8 ± 14.9, respectively (P < 0.001 for all comparisons). Mean ± SD PCDAI for inactive disease after treatment was 5.2 ± 5.4. Receiver operating characteristic (ROC) curve analysis suggested that: 1) activity of moderate/severe disease was best reflected by a PCDAI of ≥30 points, 2) clinical response (moderate/severe disease improving to mild/inactive) was best reflected by a decrease in PCDAI of ≥12.5 points, and 3) a PCDAI < 10 best reflected inactive disease. Conclusions: PCDAI scores accurately reflect disease activity as assessed by physician global assessment. A PCDAI score of ≥30 has acceptable sensitivity and specificity to indicate disease of moderate/severe activity. A PCDAI decrease of 12.5 points or greater following therapeutic intervention accurately reflects a clinically significant response. The PCDAI is an appropriate tool for intervention trials in Crohn disease in children.

Multicenter trial of d-α-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis

BACKGROUND Malabsorption and deficiency of vitamin E causing neurological degeneration are common consequences of chronic childhood cholestatic liver disease. The objective of this study was to determine the long-term efficacy and safety of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in correcting vitamin E deficiency in children with chronic cholestasis who were unresponsive to other forms of oral vitamin E. METHODS Sixty vitamin E-deficient children with chronic cholestasis unresponsive to 70-212 IU.kg-1.day-1 of oral vitamin E were entered into a trial at eight centers in the United States. After initial evaluation, treatment was started with 25 IU.kg-1.day-1 of TPGS. Vitamin E status, neurological function quantitated by a specific scoring system, and clinical and biochemical parameters were monitored during therapy. RESULTS All children responded to TPGS with normalization of vitamin E status. Neurological function, which had deteriorated before entry in the trial, improved in 25 patients, stabilized in 27, and worsened in only 2 after a mean of 2.5 years of therapy. No adverse effects were observed. CONCLUSIONS TPGS (20-25 IU.kg-1.day-1) appears to be a safe and effective form of vitamin E for reversing or preventing vitamin E deficiency during chronic childhood cholestasis.

Laboratory Values for Children With Newly Diagnosed Inflammatory Bowel Disease

OBJECTIVE. The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease. METHODS. Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospectively in 18 US/Canadian centers. Laboratory values investigated included hemoglobin level, platelet count, albumin level, and erythrocyte sedimentation rate. Disease severity was categorized by physician global assessment. RESULTS. A total of 526 children (mean age: 11.6 years; 58% male; 392 with Crohn disease and 134 with ulcerative colitis) were studied. All 4 values were normal for 21% of patients with mild Crohn disease and 54% with mild ulcerative colitis. In contrast, only 3.8% of children with moderate/severe Crohn disease and 4.3% with moderate/severe ulcerative colitis had normal results for all 4 tests. The erythrocyte sedimentation rate was least likely to be normal; overall, 26% of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate, including 18% with moderate/severe disease. Hemoglobin levels were normal for 32%, platelet counts for 50%, and albumin levels for 60%. There was no clear association between Crohn disease location and either severity or number of normal laboratory values. In contrast, there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests. CONCLUSION. The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease.

Early Volume Expansion During Diarrhea and Relative Nephroprotection During Subsequent Hemolytic Uremic Syndrome

OBJECTIVES To determine if interventions during the pre-hemolytic uremic syndrome (HUS) diarrhea phase are associated with maintenance of urine output during HUS. DESIGN Prospective observational cohort study. SETTINGS Eleven pediatric hospitals in the United States and Scotland. PARTICIPANTS Children younger than 18 years with diarrhea-associated HUS (hematocrit level <30% with smear evidence of intravascular erythrocyte destruction), thrombocytopenia (platelet count <150 × 10³/mm³), and impaired renal function (serum creatinine concentration > upper limit of reference range for age). INTERVENTIONS Intravenous fluid was given within the first 4 days of the onset of diarrhea. OUTCOME MEASURE Presence or absence of oligoanuria (urine output ≤ 0.5 mL/kg/h for >1 day). RESULTS The overall oligoanuric rate of the 50 participants was 68%, but was 84% among those who received no intravenous fluids in the first 4 days of illness. The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% confidence interval, 1.1-2.4; P = .02). Children with oligoanuric HUS were given less total intravenous fluid (r = -0.32; P = .02) and sodium (r = -0.27; P = .05) in the first 4 days of illness than those without oligoanuria. In multivariable analysis, the most significant covariate was volume infused, but volume and sodium strongly covaried. CONCLUSIONS Intravenous volume expansion is an underused intervention that could decrease the frequency of oligoanuric renal failure in patients at risk of HUS.

An Ultrastructural Study of Enteropathogenic Escherichia Coli Infection in Human Infants

Over the past 2 years, we have studied and treated 18 infants with protracted diarrhea due to an enteropathogenic Escherichia coli serogroup 0119. All patients had persistent stool escretion and jejunal over-growth with this pathogenic E. coli. Jejunal biopsy revealed atrophy of villi with a chronic inflammatory cell infiltrate in the lamina propria. E. coli 0119 adhered to the luminal surface of enterocytes. Electron microscopy showed disappearance of glycocalyx and microvilli at the areas of bacterial adherence. Intracellular damage was indicated by dilatation of rough endoplasmic reticulum, mitochondrial changes, and cytoplasmic pallor. Similar changes in histology and ultrastructure occurred in ileal epithelial cells. Glandular crypt epithelium showed prominent subnuclear vacuolation and separation of lateral intercellular junctions throughout the small intestine. Rectal mucosal biopsy showed mucus depletion and irregular atrophy of the epithelium, with E. coli 0119 adherent to the luminal surface. Ultrastructural damage paralleled that in the small intestine. E. coli 0119 causes damage to epithelial cells throughout the infant intestinal tract. This damage leads to atrophy of villi and a marked reduction in absorptive surface area, resulting in protracted diarrhea.

Grade I Reye's syndrome. A frequent cause of vomiting and liver dysfunction after varicella and upper-respiratory-tract infection.

In a one-year prospective study we assessed the incidence of Reyes syndrome in children presenting with the acute onset of vomiting after a prodromal upper-respiratory-tract infection or varicella, and with serum alanine or aspartate aminotransferase levels at least three times higher than normal, and a paucity of neurologic findings. Of 25 patients meeting the above criteria, 19 had liver biopsies yielding adequate tissue for diagnostic purposes. Biopsy specimens from 14 of these 19 patients (74 per cent) were diagnostic of Reyes syndrome, according to rigorous light-microscopical, histochemical, and ultrastructural criteria. None of the biopsy specimens contained evidence of other acute pathologic processes, including hepatitis. A wide spectrum of mitochondrial alterations existed at the ultrastructural level, ranging from mild to severe lesions that were indistinguishable from those seen in comatose patients with Reyes syndrome. Our findings suggest that the clinical complex of vomiting, hepatic dysfunction, and minimal neurologic impairment after varicella or an upper-respiratory-tract infection usually represents Reyes syndrome. This syndrome occurs more frequently than previously recognized.

Health‐related quality of life in the first year after a diagnosis of pediatric inflammatory bowel disease

Background and Aims: Assessment of health‐related quality of life (HRQOL) is of increasing importance in the evaluation of new therapies for inflammatory bowel disease (IBD). Available data concerning HRQOL in pediatric patients are sparse and uniformly cross‐sectional. The aim of this study was to describe HRQOL and influential factors in newly diagnosed pediatric patients with Crohns disease and ulcerative colitis during the first 12 months after diagnosis. Materials and Methods: Participants were drawn from a large, prospectively derived observational IBD registry of pediatric patients studied through 18 U.S. and Canadian centers. Patients who had completed a baseline IMPACT questionnaire and for whom there were 12 months of follow‐up data available were included. In addition to description of cohort, factors that were believed to influence HLQOL were assessed during the course of the year from diagnosis. Results: Two hundred eighteen children met inclusion criteria (77% Crohns disease, 23 % ulcerative colitis, mean age 12.7 ± 1.9 years). Mean total IMPACT score at baseline was 154, 181 at 6 months, and 191 at 1 year (possible range 0‐238, with increasing scores representing better quality of life). Repeated measures analysis showed that age and disease severity significantly negatively affected the IMPACT scores during the course of the year. Conclusions: In this large prospective pediatric IBD cohort, significant improvement in HRQOL is noted during the year from diagnosis. Mean IMPACT scores varied significantly depending on the disease severity and also decreased with increasing age.

Deer Sausage: A Newly Identified Vehicle of Transmission of Escherichia coli O157:H7

Five Missouri patients infected with Escherichia coli O157:H7 were studied for an epidemiologically plausible association. Case isolates, case interviews, and pathogen and meat XbaI pulsed field electrophoresis patterns were consistent with the common source being contaminated, fermented deer sausage, a previously unrecognized mode of transmission for Escherichia coli O157:H7.

Hepatobiliary sonography in cystic fibrosis

Real-time abdominal sonograms of 27 pediatric patients with cystic fibrosis were reviewed to determine the frequency of hepatobiliary abnormalities and their variation with patient age. Attention was paid to hepatic echotexture and gallbladder size and contents. Seventeen patients (63%) had abnormal livers appearing as diffuse hyperechogenicity with loss of visualization of periportal echoes in 5 of 17 patients (29%), periportal hyperechogenicity in 9 of 17 (53%) and heterogeneity in 3 of 17 (17%). Gallbladder abnormalities, including a small gallbladder and sludge, were found in 9 patients (33%). Our findings show that altered hepatic echotexture is quite common in children with cystic fibrosis. Younger children tend to have diffusely hyperechoic livers, while older children often demonstrate periportal hyperechogeneity or diffuse hepatic heterogeneity.